International Journal of Pediatrics and Adolescent Medicine 5 (2018) 142e144

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International Journal of Pediatrics and

Adolescent Medicine
journal homepage: http://www.elsevier.com/locate/ijpam

Original research article

Association of cord serum albumin with neonatal hyperbilirubinemia

among term appropriate-for-gestational-age neonates
Asit Kumar Mishra *, C. Sanyasi Naidu
Dept. of Pediatrics, Tata Main Hospital, Jamshedpur, Jharkhand, India

a r t i c l e i n f o a b s t r a c t

Article history: Introduction: Neonatal jaundice affects nearly 60% of term and 80% of preterm neonates during the first
Received 20 October 2018 week of life. Although early discharge of healthy term newborns is a common practice, neonatal
Received in revised form hyperbilirubinemia (NH) is the most common cause for readmission during the early neonatal period.
21 November 2018
Objective: To determine the association of cord serum albumin with serum bilirubin levels and whether
Accepted 6 December 2018
Available online 13 December 2018
it can be used as a risk indicator for the development of NH.
Method: In this observational study, cord blood was collected from healthy term newborns for serum
albumin level measurements. Total serum bilirubin and direct serum bilirubin were measured during 72
e96 h of life. Newborns were clinically assessed daily for NH or for any other complication during the
study period.
Result: Among the study cohort of 300 babies, 35 had a total serum bilirubin level of
17 mg/dl after 72 h
and were considered to have NH. They were grouped as Group 1, Group 2, and Group 3 according to the
cord serum albumin level 2.8 g/dl, 2.9e3.3 g/dl, and
3.4 g/dl, respectively. Statistical analysis was
conducted to assess the correlation of cord serum albumin with NH. The results showed that a cord
serum albumin level 2.8 g/dl is critical, as it was seen in 95% of term newborns who developed NH. In
the group where cord serum albumin was
3.4 g/dl, none of the term newborns developed NH.
Conclusion: Term neonates with hyperbilirubinemia with a total serum bilirubin level
17 mg/dl had
levels of cord serum albumin of 2.8 g/dl, and this can be used as a risk indicator to predict the
development of NH.
© 2018 Publishing services provided by Elsevier B.V. on behalf of King Faisal Specialist Hospital &
Research Centre (General Organization), Saudi Arabia. This is an open access article under the CC BY-NC-
ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction the newborns at risk of developing hyperbilirubinemia are identi-

Jaundice in the neonatal period is a common finding during the
first few days after birth. Approximately 3% of healthy newborns
develop jaundice with a serum bilirubin level of 15 mg/dl or higher.
Neonatal hyperbilirubinemia (NH) is a cause of concern for both
pediatricians and parents [1]. The concept of prediction offers an
attractive option to identify babies at risk of developing NH in in-
stitutions where healthy newborns are discharged within 24e48 h
of birth. Clinical examination is suggestive, but to have a diagnosis
of significant jaundice, serum bilirubin estimation is necessary. If
fied at the time of delivery, then an appropriate plan of manage-
ment can be advised for follow-up. Phototherapy can be started
early in this group of babies more effectively.
Human and animal fetuses can synthesize albumin endoge-
nously from early fetal life, starting at approximately the seventh
week of intrauterine life. Fetal liver in preterm babies can synthe-
size albumin, but they still present with hypoalbuminemia [2]. In
term babies, a serum albumin level of 2.8 g/dl is considered the
lower limit of the acceptable range [3]: mean serum albumin level
at term is 3.1 g/dl [4] and the normal range of serum albumin level
at term is 3.1 ± 3 g/dl.

2. Aim of the study

* Corresponding author. 13, Hill View Road, Northern Town, Jamshedpur, PIN
831001, India.
E-mail address: drasitmishra@gmail.com (A.K. Mishra).
The study was devised to determine the association between
Peer review under responsibility of King Faisal Specialist Hospital & Research various levels of cord serum albumin (CSA) and serum bilirubin
Centre (General Organization), Saudi Arabia. necessitating interventions in the form of exchange transfusion or

https://doi.org/10.1016/j.ijpam.2018.12.004
2352-6467/© 2018 Publishing services provided by Elsevier B.V. on behalf of King Faisal Specialist Hospital & Research Centre (General Organization), Saudi Arabia. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
 A.K. Mishra, C. Sanyasi Naidu / International Journal of Pediatrics and Adolescent Medicine 5 (2018) 142e144
phototherapy and whether it can be used as a risk indicator for
subsequent development of significant jaundice.
3. Materials and method
The present study was conducted in the neonatal unit of a large
industrial hospital in the eastern part of India. Three hundred
healthy term newborns, delivered in the hospital between February
2015 and October 2015, were considered for inclusion in the study.
The study had obtained approval from the institutional research
and ethics committee.
3.1. Inclusion and exclusion criteria
Term babies of both genders delivered both normally or by ce-
sarean section, with birth weight
2.5 kg and an Apgar score of
7/
10 at 1 min, were included. All other babies, who were at more risk
of developing jaundice because of their clinical status, were
excluded. Babies with prematurity, Rh-negative mother, septi-
cemia, delivered by instrumentation, perinatal hypoxia, breathing
difficulty, meconium aspiration syndrome, first day jaundice,
cephalohematoma, diabetic mother, and twin to twin transfusion
were excluded.
3.2. Collection of data
Parents of these babies were informed about the study, and their
consent was obtained for each baby before enrolling them in the
study. Demographic profile and relevant information was collected
using a structured proforma, which was prepared, and information
was gathered by talking to the mother and from the mother's case
sheet. Gestational age was determined by Ballard scoring and from
the mother's last menstrual period. The CSA level was estimated at
birth, and the serum bilirubin level was estimated at 72 h of life.
These babies were clinically evaluated for jaundice every day dur-
ing their nursery stay, subsequently. The serum albumin level was
estimated from 2 ml of cord blood sample collected from the
placental end, after its separation. Venous blood samples were
collected from the baby at 72e96 h of life and analyzed for total and
direct serum bilirubin and blood group.
3.3. Inference
The study outcome was designed to assess NH in newborns with
a serum bilirubin level of
17 mg/dl after 72 h of life. American
Academy of Pediatrics Practice Parameter 2004 [5] and IAP-NNF
recommend phototherapy for that level of bilirubin [6].
4. Observation
This study was conducted on a total of 300 newborns. Individual
proforma was filled for each newborn. Thirty-five neonates required
intervention in the form of phototherapy. The data were analyzed
using online calculators, http://vassarstats.net/clin1.html, http://
Table 1
Comparison of need for intervention with cord serum albumin level.
Cord albumin levels (g/dl)
2.8 (%) 2.9e3.3 (%)
Phototherapy No 83 (75.3) 93 (98.2)
Yes 33 (24.7) 2 (1.8)
Exchange transfusion No 116 (100) 95 (100)
Yes 0 (0) 0 (0)
143
vassarstats.net/odds2x2.html, and https://www.socscistatistics.
com/tests/chisquare2/Default2.aspx.
A comparison between the newborns developing significant NH
requiring phototherapy and cord albumin groups is shown in
Table 1. The observation was statistically significant, with a P
value < .00001.
The correlation of variables such as gender, mode of delivery,
oxytocin, and cord albumin level with newborns developing sig-
nificant NH requiring phototherapy is shown in Table 2. Statistical
significance was not observed in any of these variables.
CSA levels and NH were studied for any statistical association
and diagnostic predictability, and the results are shown in Table 3.
5. Discussion
NH is one of the common causes of readmissions of newborns
who were discharged early after birth and not brought back by
parents for follow-up during the next 24e48 h. There are recom-
mendations for preterm and high-risk babies, which necessitate
prolonged stay in the neonatal care unit, thus facilitating the
identification of icterus and timely intervention. Identification of
term healthy neonates, who may develop hyperbilirubinemia later,
will help in withholding their discharge from hospital or insisting
on an early follow-up visit during the next 24e48 h, thereby
facilitating optimal management of NH. We tried to assess the al-
bumin level in the cord blood as a screening tool for assessing the
risk of subsequent development of NH.
The incidence of NH was found as 11.5%. In the present study,
variables such as gender of the baby, mode of delivery, and oxytocin
induction of labor did not have significant association with subse-
quent development of NH. Observations were similar to those re-
ported in the studies by Sahu et al., in 2011 and Trivedi et al., in
2013, with statistically significant association between a CSA level
of <2.8 g/dl and subsequent development of NH.
Newborns in the group with CSA <2.8 g/dl were further
analyzed statistically, with emphasis on sensitivity, negative pre-
dictive value (NPV), Odds ratio (OR), 95% CI, and risk ratio (RR).
With a sensitivity of 94%, NPV of 98.8, OR of 27.66, and RR of 21, a
CSA of <2.8 g/dl has a good predictive value for subsequent
development of NH. These studies are compared in Table 4.
The observations of Sahu et al. [7] and Trivedi et al. [8] were
similar for the association of CSA with NH.
Thus, the CSA level appears to have a predictive value in NH. This
study indicates that a CSA level 2.8 g/dl can be considered as a
factor for the subsequent development of significant jaundice and a
level of
3.4 g/dl is safe for early discharge in the absence of other
risk factors.
6. Conclusion
Healthy full-term newborns with NH had levels of CSA of 2.8 g/
dl. Therefore, this value can be used as a risk indicator for the
prediction of subsequent development of significant jaundice,
whereas a CSA level of
3.4 g/dl can be considered safe.
Total Chi-square value c2 P value

3.4 (%)
89 (100) 265 (88.4) 51.88 <.00001
0 (0) 35 (11.6)
89 (100) 300 (100) Nil
0 (0) 0 (0)
144 A.K. Mishra, C. Sanyasi Naidu / International Journal of Pediatrics and Adolescent Medicine 5 (2018) 142e144

Table 2
Correlation of clinical variables with need for phototherapy.

Variables Phototherapy P value

No n ¼ 265 (%) Yes n ¼ 35 (%)

Gender Male 150 (56.5) 19 (55) .7949

Female 115 (43.5) 16 (45)
Mode of delivery Cesarean 77 (29.2) 10 (30) .9525
Normal vaginal 188 (70.8) 25 (70)
Oxytocin drug use No 101 (38.8) 16 (45) .386
Yes 164 (61.2) 19 (55)

Table 3
Diagnostic predictability of cord serum albumin levels for neonatal hyperbilirubinemia.

Variables Sensitivity % Specificity % PPV NPV Odds ratio (OR) Risk ratio (RR)
95% CI with range 95% CI with range

Cord albumin <2.8 g/dl 94 62.44 25 98.8 27.66, 21,

6.497e117.81 5.13e85.92
Cord albumin 2.9e3.3 g/dl 5.0 63.7 2 83.6 0.106, 0.124,
0.025e0.454 0.03e0.51
Cord albumin >3.4 g/dl 0.00 73.5 0.00 84.7 0 0

Table 4
Comparison of CSA level as a risk indicator for NH in other studies.

Studies Year Total no. of patients No. of patients with NH Cord albumin correlation with NH P value

Group 1 (CSA level in g/dl) Group 2 (CSA level in g/dl) Group 3 (CSA level in g/dl)

Sahu et al. [7] 2011 40 20 14 (<2.8 g/dl) 6 (2.9e3.3 g/dl) 0 (>3.4 g/dl) <.001
Trivedi et al. [8] 2013 605 205 120 (<2.8 g/dl 59 (2.93.3 g/dl) 26 (>3.4 g/dl) <.05
Present study 2015 300 35 33 (<2.8 g/dl 2 (2.9e3.3 g/dl) 0 (>3.4 g/dl) <.00001

Funding Formal analysis, Investigation, Writing - review & editing.

This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors. Acknowledgment

Declaration of interest The authors acknowledge the contribution from Dr Keshav

None.
Ethical statement
This work was carried out in accordance with International Code
of Medical Ethics of the World Medical Association (Declaration of
Helsinki) for experiments involving humans. Informed consent
from parents was obtained before inclusion of the babies in the
studies.
Author agreement
The authors agree and declare that this work has not been
published, that it is not under consideration for publication else-
where, that its publication is approved by all authors and tacitly or
explicitly by the responsible authorities where the work was car-
ried out, and that, if accepted, it will not be published elsewhere in
the same form, in English or any other language, including elec-
tronically, without the written consent of the copyright holder.
CRediT authorship contribution statement
Asit Kumar Mishra: Conceptualization, Methodology, Data curation,
Supervision, Validation, Writing - review & editing. C. Sanyasi Naidu:
Kumar of the Department of Beverage Research, Hochschule Gei-
senheim University, Geisenheim, Germany, for his contribution in
statistical analysis used in the manuscript. They are thankful to GM
Medical Services, Tata Main Hospital, Tata Steel, for providing
permission to submit the manuscript for publication.
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